Gordon K18 Project Summary How does the neurobiological architecture of the human brain give rise to the amazing capacities of learning language and making music? The present proposal aims to map biomarkers of rhythm and grammar traits, two skills that the PI?s preliminary work has shown to share a large proportion of variance. Furthermore, both language and music have a significant amount of heritability. Despite this, a potentially shared genetic basis, especially in the areas of rhythm and grammar, has been virtually unexplored. Rhythm is a form of communication essential not only to music but also to speech: rhythmic cues aid the listener to parse and process the grammatical aspects of sentence structure that are crucial for communicating in the spoken and written modalities. This proposal integrates diverse methodological approaches to characterize the neurobiology of rhythm at multiple levels, exploring the hypothesis that genes expressed during the development and functioning of brain networks that allow humans to perceive rhythms (both in speech and music) lead to individual differences in neural endophenotypes, which in turn influence children?s acquisition of grammatical structures. Aim 1 investigates the contribution of sensitivity to speech rhythms and musical rhythm to spoken grammar phenotypes. Aim 2 investigates shared versus separate genetic and neural architecture of rhythm and grammar phenotypes in children, using a recently developed method for imputing gene expression in brain tissue (PrediXcan). Aim 3 examines the relationship between rhythm biomarkers and the genetic architecture of communication across species. This mentored training award combines methods for behavioral phenotyping of rhythm skills in children (fine-tuned in the PI?s lab) with two cutting-edge genetics approaches (PrediXcan and Gene Set Enrichment Analysis). The innovative inter-disciplinary approach responds directly to the BRAIN Initiative?s call to integrate new technologies and approaches to map neural circuits that vary in resolution, linking activity across spatial scales from genotype to gene expression in brain tissue to behavioral phenotypes, and to discover how neural patterns are transformed into cognition and perception. By providing intensive Human Genetics research training to the PI, a Cognitive Neuroscientist, this K18 mentored training grant also fulfills the mission of the BRAIN Initiative to educate investigators across disciplines and invest in future innovations that can results from large-scale integration of data across fields, in order to address long- standing questions about how our brains allow us to communicate. Moreover, the project also lays groundwork for future pursuit of innovative brain- and genome-based diagnosis and personalized treatment of childhood language disorders (e.g., language impairment, stuttering, and dyslexia) that could potentially benefit from rhythm-based therapeutic approaches.